Prediction of Enantioseparation Efficiency of Chiral Mandelic Acid in Diastereomeric Crystallization Using a Quartz Crystal Microbalance

A quartz crystal microbalance(QCM) chiral recognition method was used to predict the chiral recognizability of a chiral selector for a racemate.The chiral selector of L-phenylalanine(L-Phe) was immobilized on the surface of a QCM sensor by a two-step assembly procedure.The L-Phe modified sensor surface was characterized using several techniques,including resonant frequency detection,the contact angle and X-ray photoelectron spectroscopy measurements.The chiral recognizability of the L-Phe-modified QCM sensor for L-mandelic acid(MA) was examined by the vapor diffused molecular assembly reaction technique,and the chiral discrimination factor between L-and D-MA was obtained to be about 8.The practical diastereomeric crystallization resolution of a MA racemic mixture was then carried out using L-Phe as resolving agent.The different properties of the diastereomer crystals of L-Phe-L-MA and L-Phe-D-MA were confirmed by HPLC,morphology and DSC detection.The factors influencing the diastereomeric crystallization resolution were investigated.Under the optimal conditions,the results showed that the diastereomeric crystallization separation of racemate MA with L-Phe as resolving agent matched well with that by the QCM chiral recognition method.Therefore,the proposed method using QCM chiral recognition can offer a simple solution to the challenge of screening a resolving agent for diastereomeric crystallization.